OBJECTIVES: Support is requested for the development of improvements to the cochlear prosthesis or cochlear implant. The cochlear implant employs electrical stimulation to activate auditory neurons in patients that have lost their hearing due to the death of inner ear sensory cells. This device is now widely used to treat the deaf, and is increasingly used for patients with residual hearing. It provides substantial benefit for both populations, but the performance of even the most successful patients is far lower than that achieved by normal hearing listeners. The proposed research program is designed to improve the cochlear implant by combining device engineering and biological approaches. RESEARCH DESIGN: Performance will be enhanced by decreasing the distance between the electrodes and cochlear neurons, so that more channels of information can be delivered, by increasing the survival of cochlear neurons, and by maintaining the neurons in contact with the implant. These goals will be achieved by producing a biological interface between the implant and the tissues of the inner ear. The prior research of this program has used primarily in vitro methods to identify factors that regulate the growth of cochlear nerve fibers and enhance neuronal survival; to evaluate the growth of neurites through three-dimensional substrates that might link a cochlear implant to the region of the spiral ganglion, and to evaluate the growth of inner ear nerve fibers on implant materials. In this application, we propose to transfer these in vitro results to the in vivo situation, using an animal model of complete sensory cell loss. This includes efficacy and materials compatibility studies, exploration of techniques to enhance growth of nerve fibers out of the spiral ganglion, and evaluation of titanium as a stable neuronal attachment and survival medium. METHODOLOGY: Guinea pigs will be deafened by the application of ototoxins. They will then be implanted with cochlear implants surrounded by hydrogels in which microchannels have been engineered to lead from the cochlear ganglion to the implant. Osmotic minipumps, cells engineered to produce neurotrophins, and layer-by-layer thin films that mediate slow release of neurotrophins, will be used to attract cochlear neuron fibers into the microchannels and to the implant. Surface engineered titanium will be used to maintain nerve fibers at the implant and enhance their survival. CLINICAL RELATIONSHIP: Disorders of hearing and balance, including SNHL, tinnitus, balance disorders and middle ear infections, are major health problems for Veterans, often resulting from damage to the ear as a consequence of military service and deployment. Future studies will include experiments with human tissue, development of a clinical device, and clinical trials. The general principles that will be studied in this program wll also be applicable to other health problems of Veterans. Improved interfaces between electrode arrays and neurons could also be applied to Veterans with visual deficits and in spinal cord injury.